The aim of this proposal is to determine the effects of intrauterine exposure to maternal stress and maternal glucocorticoids (GCs) on temperament and hypothalamic-pituitary-adrenocortical (HPA) axis regulation in two-year-old children. Although it is established that prenatal exposure to maternal stress and elevated GCs has life-long implications for health and development in animal models, the lasting impact on the human child is not known. A small, but growing literature is beginning to demonstrate that prenatal exposure to maternal stress and stress hormones has persisting influences on postnatal development. One of the primary consequences of prenatal maternal stress is an increase in behavioral inhibition or emotionality in response to challenge in the offspring. These studies, however, are often limited by their reliance on retrospective report of stress during pregnancy or parent report of child behavior and thus, may reflect differences in the ways that anxious mothers perceive their children. This project will provide the opportunity to examine prospectively and using laboratory observational measures the influence of prenatal exposure to maternal psychosocial and endocrine indicators of stress in 100 two-year-old children from pregnancies followed with serial measures from early gestation (week 14) through term and then postpartum until the age of two years. The specific aims are to: (i) Evaluate the impact of prenatal maternal psychosocial stress and maternal GCs on the development of behaviorally inhibited temperament. Behaviorally inhibited temperament will be assessed with a standardized laboratory observational measure in which children's behavioral and affective responses to a series of novel challenges is observed, (ii) Assess the influence of prenatal maternal psychosocial stress and maternal GCs on HPA axis regulation. Salivary cortisol levels will be measured at baseline and in response to a standardized laboratory challenge to evaluate the integrity of the HPA axis. Behavioral inhibition and increased stress reactivity early in childhood are likely consequences of exposure to prenatal maternal stress and are predictive of the development of anxiety disorders. A number of retrospective studies have indicated that many of the diseases of adult life have part of their origin in the prenatal period. Prospective studies, such as this one, are needed to better understand processes that might underlie this association. [unreadable] [unreadable] [unreadable]